The Quartz Crystal Microbalance (QCM) was developed and initially used to measure chemical species in a gas phase. Solution-based QCM has been a more recent development, and is largely used, e.g., as a tool in analytical electrochemistry. Using the Sauerbray equation (Sauerbray et al., Z. Physiol., 155:206-222, 1959), the QCM is capable of sensitively measuring mass changes associated with liquid-solid interfacial phenomena, particularly at electrodes. Surface bound elastic mass can be distinguished from viscoelastic behavior of bound mass or solution viscosity-density effects on the crystal frequency (f), and resistance (R), using established techniques.
Biosensors have been created using the QCM piezoelectric signal transduction mechanism, in which a range of biological macromolecules has been incorporated into the sensing system design. In some of these biosensors, whole cells have been studied on the QCM surface. Surface adherent cell types previously studied include: endothelial cells, osteoblasts, human platelets, MDCK I and II cells, 3T3 cells, CERO cells, CHO and MKE epithelial cells, and microbial biofilms (see, e.g., Marx et al., Biosens. Bioelectron., 16(9-12):773-82, 2001). These studies establish the basic principle that adherent cells produce a reversible QCM frequency (f) shift and resistance (R) shift. The cells adhere to the QCM surface to reach a steady state condition defined by stable QCM Δf and ΔR shift values in a cell-number dependent manner. Once this steady state condition has been reached, the cells within the QCM can be used as a biosensor, i.e., a whole cell QCM biosensor. However, it takes a relatively long time for the cells to reach a steady state on the QCM surface.